Intravascular Coagulation and Fibrinolysis by Stapliylocoagiilase. Comparison with Thrombin

1965 ◽  
Vol 13 (02) ◽  
pp. 457-469 ◽  
Author(s):  
J Jeljaszewicz ◽  
S Niewiarowski ◽  
A Poplawski ◽  
J Prokopowicz ◽  
K Worowski
Keyword(s):  
Intravenous Injection ◽  
Antithrombin Iii ◽  
Fibrinogen Level ◽  
Thrombin Time ◽  
Clotting Time ◽  
Short Time ◽  
Coagulation And Fibrinolysis ◽  
In Vitro Comparison

SummaryIntravascular clotting in rabbits after intravenous injection of 30 N.I.H. units of thrombin/kg and 5/mg/kg of staphylocoagulase were studied. Following determinations were made : clotting time, thrombin time, fibrinogen, factors V, VII, VIII, X, XI and XII, “true prothrombin”, two stage prothrombin, P-P test, prothrombin consumption, fibrinolysis in serum euglobulins, plasminogen, antithrombin III and VI, and coagulase reacting factor. Intravenous staphylocoagulase produced in rabbits precipitous drop of fibrinogen level in a very short time, which was not observed with the dose of thrombin used. Activity of staphylocoagulase in vivo was very much higher than of thrombin, as it could be expected on basis of the in vitro comparison. Together with defibrination caused by staphylocoagulase, fibrinogen breakdown products, identified as antithrombin VI, appear in plasma. There were no such changes observed when thrombin was used. Slight decrease of prothrombin and antithrombin III levels, together with a lack of significant changes in factors V, VII, VIII, X, XI and XII content, were observed after staphylocoagulase injection. Slight increase of CRF content in staphylo co agulase clotted plasma was noted. Fibrinolytic system was not activated during clotting process caused by staphylo-coagulase. Significance of the data obtained is discussed.

Quantitation of the Coagulation Inhibition in Vivo Due to Breakdown Products of Fibrin

1970 ◽  
Vol 23 (03) ◽  
pp. 477-485 ◽  
Author(s):  
P. S Mitchell ◽  
F. K Beller
Keyword(s):  
Blood Clotting ◽  
Fibrinogen Level ◽  
Degradation Products ◽  
Thrombin Time ◽  
Clotting Time ◽  
Human Fibrinogen ◽  
Quantitative Basis ◽  
Coagulation Inhibition

SummaryDegradation products of human fibrinogen were prepared by in vitro lysis of fibrin clots by urokinase activation and injected into rabbits on a quantitative basis. The dose necessary to anticoagulate the animal was equal to 2½ to 3 times the animals’ fibrinogen level. The effect on whole blood clotting time and thrombin time lasted for approximately 2 hrs. The “r” time of the TEG returned to normal after 1 hr while the “Max” value remained abnormal for more than 120 min. Degradation product E was shown to clear more rapidly than D by immunochemical techniques. The overall T ½ clearance was found to be approximately 12 hrs.

Effects of Heparin Oligosaccharides with High Affinity for Antithrombin III in Experimental Venous Thrombosis

1982 ◽  
Vol 47 (03) ◽  
pp. 244-248 ◽  
Author(s):  
D P Thomas ◽  
Rosemary E Merton ◽  
T W Barrowcliffe ◽  
L Thunberg ◽  
U Lindahl
Keyword(s):  
Antithrombin Iii ◽  
Specific Activity ◽  
High Specific Activity ◽  
Factor Xa ◽  
Blood Levels ◽  
Thrombin Time ◽  
High Affinity ◽  
Very High

SummaryThe in vitro and in vivo characteristics of two oligosaccharide heparin fragments have been compared to those of unfractionated mucosal heparin. A decasaccharide fragment had essentially no activity by APTT or calcium thrombin time assays in vitro, but possessed very high specific activity by anti-Factor Xa assays. When injected into rabbits at doses of up to 80 ¼g/kg, this fragment was relatively ineffective in impairing stasis thrombosis despite producing high blood levels by anti-Xa assays. A 16-18 monosaccharide fragment had even higher specific activity (almost 2000 iu/mg) by chromogenic substrate anti-Xa assay, with minimal activity by APTT. When injected in vivo, this fragment gave low blood levels by APTT, very high anti-Xa levels, and was more effective in preventing thrombosis than the decasaccharide fragment. However, in comparison with unfractionated heparin, the 16-18 monosaccharide fragment was only partially effective in preventing thrombosis, despite producing much higher blood levels by anti-Xa assays.It is concluded that the high-affinity binding of a heparin fragment to antithrombin III does not by itself impair venous thrombogenesis, and that the anti-Factor Xa activity of heparin is only a partial expression of its therapeutic potential.

A Comparison of Anticoagulation Activity of a Potent Heparin Preparation in Different Test

1979 ◽  
Author(s):  
A.S. Bhargava ◽  
J. Heinick ◽  
Chr. Schöbel ◽  
P. Günzel
Keyword(s):  
Blood Clotting ◽  
Anticoagulant Activity ◽  
Factor Xa ◽  
Thrombin Time ◽  
Beagle Dogs ◽  
Clotting Time ◽  
Relative Potencies ◽  
Heparin Preparation

The anticoagulant effect of a new potent heparin preparation was compared with a commercially available heparin in vivo after intravenous application in beagle dogs. The anticoagulant activity was determined using thrombin time, activated partial thromboplastin time and whole blood clotting time after 5, 10 and 30 minutes of application. The relative potency of the new heparin preparation (Scherinq) was found to be 1.62 to 2.52 times higher than heparin used for comparison (150 USP units/mg, Dio-synth). The anticoagulant properties of both preparations were also studied in vitro using dog and human plasma. The relative potencies in vitro correlated well with those obtained in vivo. Further characterization with amidolytic method using chromogenic substrate for factor Xa and thrombin (S-2222 and S-2238 from KABI, Stockholm) showed that heparin (Schering) contains 243 to 378 USP units/raq depending upon the test systems used to assay the anticoagulation activity and in addition, proves the validity of the amidolytic method.

Generic and Branded Versions of Argatroban Exhibit Differential Anticoagulant Effects In Whole Blood, Plasma Based Assays and Thrombin Generation Assays

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5129-5129
Author(s):  
Jawed Fareed ◽  
Debra Hoppensteadt ◽  
Omer Iqbal ◽  
Jeanine M. Walenga ◽  
Bruce E Lewis
Keyword(s):  
Protein Interactions ◽  
Whole Blood ◽  
Thrombin Generation ◽  
Conflicts Of Interest ◽  
Anticoagulant Effect ◽  
Thrombin Time ◽  
Clotting Time ◽  
Generic Products

Abstract Abstract 5129 Several generic versions of argatroban) (Mitsubishi; Tokyo, Japan) have been introduced in Japan (Argaron, Gartban, Slovastan). In addition, other generic versions of argatroban are being considered by the European and North American regulatory bodies. While the generic versions of argatroban exhibit similar antithrombin potency (Ki values), because of the differential compositional variations their anticoagulant effects in whole blood systems may differ due to their cellular and plasmatic protein interactions. Branded and generic versions of argatroban may exhibit differential anticoagulant actions in the whole blood and plasma based assays due to their differential interactions with blood cells, platelets and plasma proteins. Three generic versions of argatroban that are commercially available in Japan namely Argaron, Gartban and Slovastan and a powdered version of generic argatroban (Lundbeck) were compared with the branded argatroban. Native whole blood thrombelastographic (TEG) analysis was carried out at 0.1 ug/mL, the Activated Clotting Time (ACT) assay was carried out in a concentration range of 0–10 ug/mL, and such coagulation tests as the PT/INR, aPTT, Heptest, and calcium thrombin time were performed. Plasma retrieved from the supplemented whole blood was also assayed. Ratios of the clotting time test values from whole blood and plasma were calculated. Retrieved plasma samples were also assayed in the thrombin generation assays (TGA). All of the different versions of argatroban produced a concentration dependent anticoagulant effect in the native whole blood TEG and ACT. In the TEG, while argatroban and Slovastan showed a similar effect, Gartban, Argaron and a powdered generic showed weaker effects. Argatroban was also different in the ACT assay. At a concentration of 5 ug/ml the ACTs were, Arg 340+15.2 secs, S 297+10.5 secs, G 292.0+19.1 secs and A 285.2+21.7 secs. In the citrated whole blood systems, all agents produced a concentration dependent anticoagulant effect; however, the generic versions produced a stronger anticoagulant effect in comparison to branded argatroban (p<0.001). In the PT assay at 5 ug/mL, argatroban showed 32 ± 3 sec vs 40–50 sec for the generic products. Similarly in the aPTT, Heptest and thrombin time tests argatroban was weaker than the generic products. Differences among generic versions were also evident. Similar results were obtained in the retrieved plasma, however the ratio of whole blood over plasma varied from product to product. The IC50 of the generic and branded argatrobans in the TGA were also different. These results show that while in the thrombin inhibition assays generic and branded argatroban may show similar effects, these agents exhibit assay dependent differences in the whole blood and plasma based assays. Such differences may be more evident in the in vivo studirs where endothelial cells and other interactions may contribute to product individuality. Therefore, based on the in vitro antiprotease assays, generic argatrobans may not be considered equivalent and require a multi-parametric study. Currently available generic argatrobans may not be equivalent in the in vivo anticoagulant effects. Therefore, clinical validation of the clinical equivalence for these drugs is warranted. Disclosures: No relevant conflicts of interest to declare.

Bleeding in Uremic Patients after Carbenicillin

1976 ◽  
Vol 36 (01) ◽  
pp. 115-126 ◽  
Author(s):  
K Andrassy ◽  
E Weischedel ◽  
E Ritz ◽  
T Andrassy
Keyword(s):  
Platelet Function ◽  
Antithrombin Iii ◽  
Serum Levels ◽  
Coagulation Factors ◽  
Coagulation System ◽  
Hemorrhagic Diathesis ◽  
Thrombin Time ◽  
Antithrombin Iii Activity

SummaryHemorrhagic diathesis was observed in patients with renal insufficiency after carbenicillin at serum levels > 300 μg/ml. Normal coagulation factors (F. I, II, V, VII, VIII, X), normal PTT, normal platelet counts, negative ethanol gelation test (fibrin monomers) were found as well as a prolongation of thromboplastin time (Quick), thrombin time, reptilase time and thrombin coagulase time. Platelet function was disturbed. In addition, the plasmatic system was involved: inhibition of fibrinogen-fibrin conversion (Belitser assay) and enhanced antithrombin III activity; in vivo the latter was ascribed to a heparin-like activity. In vitro, abnormal fibrinogen-fibrin conversion and a modified electrophoretic mobility of antithrombin III was seen: however an enhanced antithrombin III activity in vitro was not found with carbenicillin and various penicillin derivatives.This study demonstrates that carbenicillin, in addition to its known effect on platelet function, also disturbs the plasmatic coagulation system. This additional effect of carbenicillin is clinically important since protamin chloride effectively blocks bleeding without interfering with antibacterial activity.Both penicillin and penicillin derivatives have been shown to interfere with hemostasis and to cause clinically manifest hemorrhagic diathesis (Fleming and Fish 1947, Lurie et al. 1970a, b, McClure et al. 1970, Yudis et al. 1972, Demos 1971, Waisbren et al. 1971). Carbenicillin interferes with ADP-, collagen- or thrombin-induced platelet aggregation and with the release reaction both in vivo (McClure et al. 1970, Cazenave et al. 1973) and in vitro (McClure et al. 1970, Cazenave et al. 1973). In addition Lurie and colleagues (1970b) concluded that an inhibition of the conversion of fibrinogen to fibrin is involved although no experimental details were given. Later Brown and colleagues (1974) concluded that carbenicillin at usual dose levels “only affects the platelet component of hemostasis and has little effect on fibrin formation or other phases of coagulation in patients with normal renal function”.

scholarly journals Effect of Angiography on Blood Coagulation

1977 ◽  
Author(s):  
W. H. Krause ◽  
A. Lang
Keyword(s):  
Contrast Media ◽  
Prothrombin Time ◽  
Antithrombin Iii ◽  
Degradation Products ◽  
Anticoagulant Activity ◽  
Thromboembolic Complication ◽  
Thrombin Time ◽  
Media Concentration

It is known, that angiographic contrast media have an anticoagulant activity in vitro. The purpose of the present study was, to investigate this effect in vivo. The catheter was introduced percutaneously according to Seldinger into the femoral artery. The prothrombin time, activated thromboplastin time (APTT), thrombin time, reptilase time, fibrinogen, plasminogen, antithrombin III, platelets, fibrin/fibrinogen degradation products (FDP), haematocrit and contrast media concentration were studied in a series of 50 patients before and following abdominal aorto-arteriographic procedures up to 6 hours. Thrombin time and reptilase time were prolonged significantly 30 and 60 minutes after angiography. There was a correlation between clotting tiies and contrast media concentrations. Prothrombin time, APTT, and platelet counts remained unchanged. Fibrinogen, plasminogen,and antithrombin III levels showed a significant reduction after 30 minutes. FDP concentrations were increased significantly up to 6 hours, there was no correlation between contrast media concentrations and split products. The results were corrected for contrast media dilution according to the haematocrit. No thromboembolic complication was observed. The results suggest that angiographic procedure may initiate an intravascular coagulation with an activation of the fibrinolytic system. In addition the contrast media showed an inhibition of fibrin polymerization in vivo.

Lupus-Like Anticoagulant In A Patient With Severe Factor VIII Deficiency

1981 ◽  
Author(s):  
R S Weinger ◽  
J L Moake ◽  
D Deykin ◽  
A Lopez ◽  
J D Olson
Keyword(s):  
Fibrinogen Level ◽  
Specific Inhibitor ◽  
Test System ◽  
Rabbit Brain ◽  
Clotting Time ◽  
Normal Plasma ◽  
Tissue Thromboplastin ◽  
Dilute Suspension

A severe hemophiliac (<1% FVIII-AHG) was transfused with FVIII concentrate and had orthopedic surgery without complication. His in vivo FVIII-AHG survival was normal (T½= 8hrs), as was his fibrinogen level, prothrombin (PT) and thrombin times. His prolonged (>100 sec.) activated partial thromboplastin time was incompletely corrected (40 sec.; normal<36 sec.) by the in vitro addition of an equal volume of pooled normal plasma, and did not become further prolonged after ½ and 2 hr. incubations at 37°C. A specific inhibitor to FVIII-AHG was not present. However, a thromboplastin inhibition test using patient plasma and progressively higher dilutions of rabbit brain thromboplastin (whole phospholipoprotein membranes) in a PT test system was positive. When either normal gel-separated platelets (GSP) or a dilute suspension of inosithin was used as a source of phospholipid, and clotting then initiated by the simultaneous addition of calcium and Russell’s viper venom (to activate FX directly), patient plasma clotting times were similar to the clotting times of normal plasma and other severe FVIII-AHG deficient plasmas. In contrast, when both normal GSP and dilutions of tissue thromboplastin reagent were added to plasma, and clotting then initiated by recalcification, patient plasma clotting time was prolonged in comparison to the clotting times of normal plasma and other FVIII-AHG deficient plasmas. This “lupus-like” anticoagulant had no effect on in vivo hemostasis, even in our patient with severe hemophilia A. The anticoagulant differs from a lupus anticoagulant recently well characterized (Thiagarajan et al., J.Clin. Invest. 66;397,1980) in that it interacts better with phospholipoprotein membranes than with free phospholipids, and the in vitro defect is not corrected by the addition of normal platelets.

scholarly journals A Comparative Study of the Effects of Heparin and a Low Molecular Weight Semi-Synthetic Heparin Analogue Upon Platelet Function

1977 ◽  
Author(s):  
R. Michalski ◽  
D. A. Lane ◽  
V. V. Kakkar
Keyword(s):  
Molecular Weight ◽  
Intravenous Injection ◽  
Platelet Function ◽  
Factor Xa ◽  
In Vitro Tests ◽  
Low Molecular Weight ◽  
Clotting Time ◽  
Induced Aggregation

We have already reported O) some in vitro and in vivo properties of a low molecular weight glycosaminoglycan polysulphate. It was found that while this semi-synthetic heparin analogue (SSHA) was virtually inactive in a number of in vitro clotting assays, following intravenous or subcutaneous injection it has a more specific anti-Xa potentiating effect than heparin. In the present communication a comparison has been made of some effects of SSHA and heparin upon platelet function. In several of the in vitro tests performed, such as their potentiating effect on ADP and adrenaline induced aggregation and their effects on the aggregation of washed platelets by Factor Xa, heparin proved to be far more potent than SSHA. It was found that after intravenous injection of both drugs, PRP samples containing comparable anti-Factor Xa activities responded differently to the addition of thrombin as SSHA barely inhibited thrombin induced aggregation. Similarly, SSHA had little effect on the dilute thrombin clotting time of plasma, following intravenous injection. Heparin and analogue were neutralised to approximately the same degree by a crude PF4 preparation, and similar transient thrombocytopenia effects were observed with both drugs.

Effects of Bradykinin on Coagulation and Fibrinolysis Study in Vitro and in Vivo

1965 ◽  
Vol 14 (03/04) ◽  
pp. 508-518 ◽  
Author(s):  
G. G Neri Serneri ◽  
P. L Rossi Ferrini ◽  
P Paoletti ◽  
A Panti ◽  
G D’Ayala Valva
Keyword(s):  
Thrombin Generation ◽  
Thrombin Time ◽  
Lysis Time ◽  
Time Determination ◽  
Recalcification Time ◽  
Generation Test ◽  
Coagulation And Fibrinolysis

SummaryThe effects of bradykinin on coagulation and fibrinolysis have been studied both “in vitro” and “in vivo” in man. “In vitro” bradykinin employed at different concentrations does not affect the coagulation and fibrinolysis processes in any appreciable way. Bradykinin, intraarterially injected in man in the dose of 10 y, does not modify coagulation studied both with global investigations (thrombelastogram, recalcification time) and with analytical researches (Quick’s time, activation test of intrinsic thromboplastin, thrombin generation test and thromboplastin test, thrombin time, determination of antithrombin II and III). Bradykinin instead produces an activation of fibrinolysis both in the thrombelastographic investigation and in the lysis time of euglobulins. The decrease in the activity of the proactivator and of plasminogen supports our view that bradykinin produces an activation of the fibrinolytic system by liberating tissue kinases which act on the proactivator. The authors have discussed the physiological and physiopathological significance of the observed findings.

Comparison of the Anticoagulant and Antithrombotic Effects of Synthetic Thrombin and Factor Xa Inhibitors

1990 ◽  
Vol 63 (02) ◽  
pp. 220-223 ◽  
Author(s):  
J Hauptmann ◽  
B Kaiser ◽  
G Nowak ◽  
J Stürzebecher ◽  
F Markwardt
Keyword(s):  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Factor Xa Inhibitors ◽  
Venous Stasis ◽  
Clotting Time ◽  
Thrombosis Model ◽  
Activity Factor ◽  
Antithrombotic Effects

SummaryThe anticoagulant effect of selected synthetic inhibitors of thrombin and factor Xa was studied in vitro in commonly used clotting assays. The concentrations of the compounds doubling the clotting time in the various assays were mainly dependent on their thrombin inhibitory activity. Factor Xa inhibitors were somewhat more effective in prolonging the prothrombin time compared to the activated partial thromboplastin time, whereas the opposite was true of thrombin inhibitors.In vivo, in a venous stasis thrombosis model and a thromboplastin-induced microthrombosis model in rats the thrombin inhibitors were effective antithrombotically whereas factor Xa inhibitors of numerically similar IQ value for the respective enzyme were not effective at equimolar dosageThe results are discussed in the light of the different prelequisiles and conditions for inhibition of thrombin and factor Xa in the course of blood clotting.

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